We plan to continue, as well as to initiate research in the following areas: (1) To study the dopamine (DA) receptors at the molecular level. The solubilized striatal DA receptors will be further purified and characterized. The purified antigens will be used for production of specific monoclonal and/or polyclonal antibodies. (2) The turnover rates of normosensitive, subsensitive and supersensitive striatal DA receptor subtypes will be studied. The recovery rates of the functional DA receptors will be assessed by behavioral and biochemical tests. (3) The effects of selective and non-selective DA agonists on extrapyramidal dysfunctions in monkeys with unilateral ventromedial tegmental lesions of the brain stem and in NMPTP-treated monkeys will be investigated. The biochemical, histochemical and neurological deficits in the two non-human primate models which mimic Parkinson's disease will be studied. (4) The interactions of DA agonists with pre- and postsynaptic (normosensitive and supersensitive) DA receptor subtypes will be evaluated. (5) The involvement of the dopaminergic neuronal system in the compulsive self-mutilative biting behavior will be studied in rats and monkeys with supersensitive DA receptors. The role of DA and of other neurotransmitters in the neuropathology of Lesch-Nyhan syndrome will be investigated.